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MiRNA profiling of whole trabecular bone: identification of osteoporosis-related changes in MiRNAs in human hip bones

BACKGROUND: MicroRNAs (miRNAs) are important regulators of gene expression, with documented roles in bone metabolism and osteoporosis, suggesting potential therapeutic targets. Our aim was to identify miRNAs differentially expressed in fractured vs nonfractured bones. Additionally, we performed a mi...

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Autores principales: De-Ugarte, Laura, Yoskovitz, Guy, Balcells, Susana, Güerri-Fernández, Robert, Martinez-Diaz, Santos, Mellibovsky, Leonardo, Urreizti, Roser, Nogués, Xavier, Grinberg, Daniel, García-Giralt, Natalia, Díez-Pérez, Adolfo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4640351/
https://www.ncbi.nlm.nih.gov/pubmed/26555194
http://dx.doi.org/10.1186/s12920-015-0149-2
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author De-Ugarte, Laura
Yoskovitz, Guy
Balcells, Susana
Güerri-Fernández, Robert
Martinez-Diaz, Santos
Mellibovsky, Leonardo
Urreizti, Roser
Nogués, Xavier
Grinberg, Daniel
García-Giralt, Natalia
Díez-Pérez, Adolfo
author_facet De-Ugarte, Laura
Yoskovitz, Guy
Balcells, Susana
Güerri-Fernández, Robert
Martinez-Diaz, Santos
Mellibovsky, Leonardo
Urreizti, Roser
Nogués, Xavier
Grinberg, Daniel
García-Giralt, Natalia
Díez-Pérez, Adolfo
author_sort De-Ugarte, Laura
collection PubMed
description BACKGROUND: MicroRNAs (miRNAs) are important regulators of gene expression, with documented roles in bone metabolism and osteoporosis, suggesting potential therapeutic targets. Our aim was to identify miRNAs differentially expressed in fractured vs nonfractured bones. Additionally, we performed a miRNA profiling of primary osteoblasts to assess the origin of these differentially expressed miRNAs. METHODS: Total RNA was extracted from (a) fresh femoral neck trabecular bone from women undergoing hip replacement due to either osteoporotic fracture (OP group, n = 6) or osteoarthritis in the absence of osteoporosis (Control group, n = 6), matching the two groups by age and body mass index, and (b) primary osteoblasts obtained from knee replacement due to osteoarthritis (n = 4). Samples were hybridized to a microRNA array containing more than 1900 miRNAs. Principal component analysis (PCA) plots and heat map hierarchical clustering were performed. For comparison of expression levels, the threshold was set at log fold change > 1.5 and a p-value < 0.05 (corrected for multiple testing). RESULTS: Both PCA and heat map analyses showed that the samples clustered according to the presence or absence of fracture. Overall, 790 and 315 different miRNAs were detected in fresh bone samples and in primary osteoblasts, respectively, 293 of which were common to both groups. A subset of 82 miRNAs was differentially expressed (p < 0.05) between osteoporotic and control osteoarthritic samples. The eight miRNAs with the lowest p-values (and for which a validated miRNA qPCR assay was available) were assayed, and two were confirmed: miR-320a and miR-483-5p. Both were over-expressed in the osteoporotic samples and expressed in primary osteoblasts. miR-320a is known to target CTNNB1 and predicted to regulate RUNX2 and LEPR, while miR-483-5p down-regulates IGF2. We observed a reduction trend for this target gene in the osteoporotic bone. CONCLUSIONS: We identified two osteoblast miRNAs over-expressed in osteoporotic fractures, which opens novel prospects for research and therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12920-015-0149-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-46403512015-11-11 MiRNA profiling of whole trabecular bone: identification of osteoporosis-related changes in MiRNAs in human hip bones De-Ugarte, Laura Yoskovitz, Guy Balcells, Susana Güerri-Fernández, Robert Martinez-Diaz, Santos Mellibovsky, Leonardo Urreizti, Roser Nogués, Xavier Grinberg, Daniel García-Giralt, Natalia Díez-Pérez, Adolfo BMC Med Genomics Research Article BACKGROUND: MicroRNAs (miRNAs) are important regulators of gene expression, with documented roles in bone metabolism and osteoporosis, suggesting potential therapeutic targets. Our aim was to identify miRNAs differentially expressed in fractured vs nonfractured bones. Additionally, we performed a miRNA profiling of primary osteoblasts to assess the origin of these differentially expressed miRNAs. METHODS: Total RNA was extracted from (a) fresh femoral neck trabecular bone from women undergoing hip replacement due to either osteoporotic fracture (OP group, n = 6) or osteoarthritis in the absence of osteoporosis (Control group, n = 6), matching the two groups by age and body mass index, and (b) primary osteoblasts obtained from knee replacement due to osteoarthritis (n = 4). Samples were hybridized to a microRNA array containing more than 1900 miRNAs. Principal component analysis (PCA) plots and heat map hierarchical clustering were performed. For comparison of expression levels, the threshold was set at log fold change > 1.5 and a p-value < 0.05 (corrected for multiple testing). RESULTS: Both PCA and heat map analyses showed that the samples clustered according to the presence or absence of fracture. Overall, 790 and 315 different miRNAs were detected in fresh bone samples and in primary osteoblasts, respectively, 293 of which were common to both groups. A subset of 82 miRNAs was differentially expressed (p < 0.05) between osteoporotic and control osteoarthritic samples. The eight miRNAs with the lowest p-values (and for which a validated miRNA qPCR assay was available) were assayed, and two were confirmed: miR-320a and miR-483-5p. Both were over-expressed in the osteoporotic samples and expressed in primary osteoblasts. miR-320a is known to target CTNNB1 and predicted to regulate RUNX2 and LEPR, while miR-483-5p down-regulates IGF2. We observed a reduction trend for this target gene in the osteoporotic bone. CONCLUSIONS: We identified two osteoblast miRNAs over-expressed in osteoporotic fractures, which opens novel prospects for research and therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12920-015-0149-2) contains supplementary material, which is available to authorized users. BioMed Central 2015-11-10 /pmc/articles/PMC4640351/ /pubmed/26555194 http://dx.doi.org/10.1186/s12920-015-0149-2 Text en © De-Ugarte et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
De-Ugarte, Laura
Yoskovitz, Guy
Balcells, Susana
Güerri-Fernández, Robert
Martinez-Diaz, Santos
Mellibovsky, Leonardo
Urreizti, Roser
Nogués, Xavier
Grinberg, Daniel
García-Giralt, Natalia
Díez-Pérez, Adolfo
MiRNA profiling of whole trabecular bone: identification of osteoporosis-related changes in MiRNAs in human hip bones
title MiRNA profiling of whole trabecular bone: identification of osteoporosis-related changes in MiRNAs in human hip bones
title_full MiRNA profiling of whole trabecular bone: identification of osteoporosis-related changes in MiRNAs in human hip bones
title_fullStr MiRNA profiling of whole trabecular bone: identification of osteoporosis-related changes in MiRNAs in human hip bones
title_full_unstemmed MiRNA profiling of whole trabecular bone: identification of osteoporosis-related changes in MiRNAs in human hip bones
title_short MiRNA profiling of whole trabecular bone: identification of osteoporosis-related changes in MiRNAs in human hip bones
title_sort mirna profiling of whole trabecular bone: identification of osteoporosis-related changes in mirnas in human hip bones
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4640351/
https://www.ncbi.nlm.nih.gov/pubmed/26555194
http://dx.doi.org/10.1186/s12920-015-0149-2
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